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Biomedical subjects

C Fordham von Reyn

Publications and source records attributed to C Fordham von Reyn.

At least 19 recordsLinked to original sources
PubMed2006

Baseline mycobacterial immune responses in HIV-infected adults primed with bacille Calmette-Guérin during childhood and entering a tuberculosis booster vaccine trial.

BACKGROUND: Most new tuberculosis vaccines will be administered as a booster to subjects primed with bacille Calmette-Guérin (BCG) during childhood. METHODS: We investigated in vivo and in vitro immune responses to mycobacteria in human immunodeficiency virus (HIV)-positive subjects in Tanzania primed with BCG during childhood and entering a tuberculosis booster vaccine trial. Tests included intradermal skin testing for Mycobacterium tuberculosis purified protein derivative (PPD) and Mycobacterium avium sensitin (MAS); lymphocyte proliferation assays and interferon (IFN)-gamma levels after stimulation with Mycobacterium vaccae sonicate (MVS), M. tuberculosis early secreted antigen (ESAT)-6, M. tuberculosis antigen 85 (Ag85), or M. tuberculosis whole-cell lysate (WCL); and determination of serum antibody to lipoarabinomannin (LAM). RESULTS: A total of 888 subjects with CD4 cell counts > or = 200 cells/mm3 were enrolled. PPD and MAS test results were positive in 34% and 30% of the subjects, respectively. Proliferative responses were detected as follows: MVS, 6%; Ag85, 24%; ESAT-6, 21%; and WCL, 59%. IFN-gamma responses were 2%, 6%, 12%, and 38%, respectively. LAM antibody was detected in 28% of the subjects. Subjects were more likely to have detectable proliferative and IFN-gamma responses if they had positive PPD test results or CD4 cell counts > or = 500 cells/mm3. Overall, 94% of the subjects had evidence of primed mycobacterial immune responses. CONCLUSION: Of HIV-positive BCG-immunized adults with CD4 cell counts > or = 200 cells/mm3 in Tanzania, 94% are primed for booster mycobacterial immunization.

Adult↗
PubMed2006

Environmental risk factors for infection with Mycobacterium avium complex.

Infection with Mycobacterium avium complex is acquired from the environment, but risk factors for M. avium complex infection and disease are poorly understood. To identify risk factors for infection, the authors performed a 1998-2000 cross-sectional study in western Palm Beach County, Florida, using a population-based random household survey. M. avium complex infection was identified by use of the M. avium sensitin skin test. Of 447 participants, 147 (32.9%) had a positive test reaction, 186 (41.6%) had a negative test reaction, and, for 114 (25.5%), test results were indeterminate. Among the 333 participants with positive or negative M. avium sensitin skin tests, age-adjusted independent predictors of M. avium complex infection in a multivariate model included Black race (odds ratio = 3.8, 95% confidence interval: 2.2, 6.6), birth outside the United States (odds ratio = 2.1, 95% confidence interval: 1.1, 3.9), and more than 6 years' cumulative occupational exposure to soil (odds ratio = 2.7, 95% confidence interval: 1.3, 6.0). Exposure to water, food, or pets was not associated with infection. Results indicate that soil is a reservoir for M. avium complex associated with human infection and that persons whose occupations involve prolonged soil exposure are at increased risk of M. avium complex infection.

AIDS-Related Opportunistic Infections↗
PubMed2005

High rates of clinical and subclinical tuberculosis among HIV-infected ambulatory subjects in Tanzania.

BACKGROUND: We sought to determine the prevalence of active tuberculosis among ambulatory HIV-infected persons in Tanzania with CD4 cell counts of > or =200 cells/mm3 and a bacille Calmette-Guerin vaccination scar. METHODS: Subjects who volunteered for a tuberculosis booster vaccine trial were screened for active tuberculosis by obtainment of a history, physical examination, chest radiography, sputum culture and acid fast bacillus (AFB) stain, and blood culture. All subjects underwent a tuberculin skin test (TST) and lymphocyte proliferation assays (LPAs) for detection of responses to mycobacterial antigens. RESULTS: Active tuberculosis was identified at baseline in 14 (15%) of the first 93 subjects who were enrolled: 10 (71%) had clinical tuberculosis (symptoms or chest radiograph findings), and 4 (29%) had subclinical tuberculosis (positive sputum AFB stain or culture results but no symptoms or chest radiograph findings). An additional 6 subjects with subclinical tuberculosis were identified subsequently. The 10 subjects with subclinical tuberculosis included 3 with positive sputum AFB stains results and 7 who were only identified by a positive sputum culture result. Compared with subjects who did not have tuberculosis, the 10 subjects with subclinical tuberculosis were more likely to have peripheral lymphadenopathy, positive TST results, and elevated LPA responses to early secreted antigenic target-6 (ESAT). Eight of 10 patients had received isoniazid because of a positive TST result before active tuberculosis was recognized. CONCLUSIONS: Clinical and subclinical tuberculosis are common among ambulatory HIV-infected persons, and some cases can only be identified by sputum culture. World Health Organization guidelines for screening for latent tuberculosis before treatment do not recommend sputum culture and, therefore, may fail to identify a substantial number of HIV-infected persons with subclinical, active tuberculosis.

Adult↗
PubMed2004

Antibody responses to intradermal recombinant hepatitis B immunization among HIV-positive subjects.

We conducted a randomized, controlled clinical trial to determine the immunogenicity of intradermal immunization with recombinant hepatitis B vaccine among HIV-positive subjects. Induction of antibody concentration over 10 IU/L or four-fold increase in the antibody concentration against hepatitis B surface antigen was regarded a successful immunization. Intradermal immunization induced protective immunity in 39% of participants who received three doses of recombinant hepatitis B vaccine. Intradermal immunization may provide a way to improve the outcome of hepatitis B vaccination among HIV-infected persons. Three doses of intradermal immunization alone induces protective immunity against hepatitis B as often as intramuscular immunization.

Adult↗
PubMed2004

Recent trends in infective endocarditis: influence of case definitions.

PURPOSE OF REVIEW: Infective endocarditis continues to pose major challenges in diagnosis and management despite advances in understanding the epidemiology, microbiology, and pathology of the disease. The purpose of this article is to provide a review of diagnosis, microbiology, and treatment of infective endocarditis, particularly as they are influenced by case definitions. RECENT FINDINGS: Case definitions have a critical effect on the interpretation of trends in infective endocarditis, and recent studies have proposed more specific criteria. Studies have also addressed the appropriate use of echocardiography to assist in the diagnosis and management of infective endocarditis. Staphylococcus aureus has become an increasingly common cause of infective endocarditis, and the microbiology of nosocomial infective endocarditis is changing. Newer techniques are being used to aid in the identification of causal agents in blood culture-negative infective endocarditis. Antimicrobial guidelines for the treatment of infective endocarditis are readily available, including a proposal to avoid premature discharge of patients on outpatient antibiotic therapy. Additional studies have been conducted on combination antibiotic therapy, duration of treatment, dosing of aminoglycosides, alternative agents for gram-positive organisms, aspirin therapy, and surgical interventions. SUMMARY: Recent trends in diagnosis, microbiology, and treatment of infective endocarditis are described, and case definitions play a critical role in their interpretation.

Anti-Bacterial Agents↗
PubMed2003

Immunogenicity of an inactivated mycobacterial vaccine for the prevention of HIV-associated tuberculosis: a randomized, controlled trial.

OBJECTIVE: Prior to the widespread use of Mycobacterium bovis, Bacille Calmette-Guerin (BCG), inactivated whole cell mycobacterial vaccines had been shown effective in the prevention of tuberculosis. The present study was conducted to determine the safety and immunogenicity of an inactivated whole cell mycobacterial vaccine in persons with HIV infection.DESIGN Randomized, controlled trial. METHODS: A total of 39 HIV-positive patients with prior BCG immunization and CD4 cell counts >/= 200 x 10(6) cells/l were randomized to five doses of inactivated Mycobacterium vaccae (MV) vaccine or control vaccine (CV). Lymphocyte proliferation (LPA) and interferon gamma (IFN-gamma) responses to mycobacterial antigens were assayed at baseline, after three and five doses of vaccine and > 1 year later. Parallel studies were conducted in 10 HIV-negative subjects with prior BCG immunization. RESULTS: Among HIV-positive patients, 19 MV recipients had higher LPA and IFN-gamma responses to MV sonicate than 20 CV recipients after three and five doses of vaccine and > 1 year later. LPA responses to Mycobacterium tuberculosis whole cell lysate increased over time in both groups consistent with prior BCG immunization and current antiretroviral therapy; after three doses, responses were boosted to higher levels in MV subjects than CV subjects. LPA responses to WCL were also boosted in HIV-negative MV recipients. Immunization was safe and had no adverse effects on HIV viral load or CD4 cell count. CONCLUSIONS: In BCG-primed, HIV-positive and HIV-negative subjects, MV induces durable cellular immune responses to a new mycobacterial antigen and boosts pre-existing responses to WCL. MV is a candidate for clinical trials for the prevention of HIV-associated tuberculosis.

Adult↗
PubMed2003

Fish tank exposure and cutaneous infections due to Mycobacterium marinum: tuberculin skin testing, treatment, and prevention.

In the present study, 8 patients with soft tissue infection due to Mycobacterium marinum are described, and contemporary data on treatment are reviewed. Six patients had positive cultures, all patients had cutaneous exposure to fish tanks, 7 had sporotrichoid lesions, and 2 had deep infection. All 7 tested patients had tuberculin skin test reactions > or =10 mm. Six patients with disease limited to the skin were successfully treated with 2-drug combination therapy, including clarithromycin, ethambutol, and rifampin. Optimal treatment should include 2 drugs for 1-2 months after resolution of lesions, typically 3-4 months in total. Deeper infections may require more prolonged treatment and surgical debridement. Positive tuberculin reactions may be due to infection with M. marinum. Persons with open skin lesions or immunosuppression should avoid cutaneous contact with fish tanks.

Adult↗
PubMed2003

Detection of latent tuberculosis among HIV-infected patients after initiation of highly active antiretroviral therapy.

This cross-sectional study of 110 individuals examined skin testing for latent tuberculosis infection (LTBI) after the initiation of highly active antiretroviral therapy. Skin test reactivity to one or more of four antigens was found in 98 out of 110 subjects (89%), and was maximal in those whose CD4 cell counts recovered to >= 100 cells/mm3. Skin testing is reliable for the identification or exclusion of LTBI once the CD4 cell count recovers to >= 100 cells/mm3.

AIDS-Related Opportunistic Infections↗
PubMed2003

Dual skin testing for latent tuberculosis infection: a decision analysis.

BACKGROUND: Recent data indicate that 10- to 14-mm Mycobacterium tuberculosis purified protein derivative (PPD) reactions are often due to prior infections with nontuberculous mycobacteria. Therefore, use of a 10-mm cutpoint to define latent tuberculosis infection (LTBI) results in false-positive diagnoses and unnecessary treatment for LTBI. A second skin test, Mycobacterium avium sensitin (MAS), has been shown to accurately identify false-positive PPD results. OBJECTIVE: To compare the costs and accuracy of a single skin-test strategy (SST) with PPD alone with a dual skin-test strategy (DST) where 10- to 14-mm PPD results are also tested with MAS. METHODS: A decision analytic model was developed to evaluate the two strategies. The model accounted for the costs of skin testing, the costs of LTBI treatment, the costs of undetected LTBI, and the sensitivity and specificity of each strategy. RESULTS: We estimated that DST saved US dollars 3 per subject tested compared to SST. Savings were due to a reduction in false-positive PPD results and consequent reduction in unnecessary treatment for LTBI of >60%. The DST strategy was associated with a minimal increase in undetected LTBI (6% vs 7%). Results were stable for a broad range of parameter values. CONCLUSIONS: DST is a promising approach to improving the specificity of LTBI testing when a 10-mm PPD cutpoint is used and would reduce costs and unnecessary drug treatment.

Costs and Cost Analysis↗
PubMed2003

Utility of dual skin tests to evaluate tuberculin skin test reactions of 10 to 14 mm in healthcare workers.

OBJECTIVE: To define the utility of 10- to 14-mm reactions to a Mycobacterium tuberculosis purified protein derivative (PPD) skin test for healthcare workers (HCWs). DESIGN: Blinded dual skin testing, using PPD and M. avium sensitin, of HCWs at a single medical center who had a 10- to 14-mm reaction to PPD when tested by personnel from the Occupational Health Department as part of routine annual screening. SETTING: A single tertiary-care academic medical center. PARTICIPANTS: Employees of the medical center who underwent routine annual PPD screening and were identified by the Occupational Health Department as having a reaction of 10 to 14 mm to PPD. RESULTS: Nineteen employees were identified as candidates and 11 underwent dual skin testing. Only 4 (36%) had repeat results for PPD in the 10- to 14-mm range, whether read by Occupational Health Department personnel or study investigators. For only 5 (45%) of the subjects did the Occupational Health Department personnel and study investigators concur (+/- 3 mm) on the size of the PPD reaction. Two of the 4 subjects with reactions of 10 to 14 mm as measured by the study investigators were M. avium sensitin dominant, 1 was PPD dominant, and 1 was nondominant. CONCLUSION: A reaction of 10 to 14 mm to PPD should not be used as an indication for the treatment of latent tuberculosis (TB) infection in healthy HCWs born in the United States with no known exposure to TB.

Hospitals, University↗
PubMed2003

A cost-effectiveness analysis of universal versus selective immunization with Mycobacterium bovis bacille Calmette-Guérin in Finland.

SETTING: Mycobacterium bovis bacille Calmette-Gueŕin (BCG) is provided to all infants born in Finland. OBJECTIVE: To analyze the cost-effectiveness of universal versus selective BCG immunization. DESIGN: A Markov model was developed to simulate rates of tuberculosis (TB) and non-tuberculous mycobacterial disease (NTM), and to examine the cost-effectiveness in terms of cost per case averted of three different strategies: universal BCG, selective BCG (10% of infants at higher TB risk than other infants) or no BCG immunization. RESULTS: In a cohort of 60,000 infants over 15 years, the model predicts five cases each of TB and NTM disease with universal immunization, 8-21 TB and 31 NTM cases with various strategies of selective immunization, and 25 TB and 34 NTM cases with no BCG immunization. BCG side-effects are predicted in 5, 0.5 and 0 infants, respectively. The cost per case averted for immunization strategies ranges from a cost of 38,311 US dollars to a savings of 323 dollars as selective immunization becomes more efficient at targeting infants at highest risk of TB. CONCLUSIONS: In a country with a low incidence of pediatric tuberculosis, selective BCG immunization is a more cost-effective strategy than universal BCG immunization for the prevention of tuberculosis, but results in an increase in NTM cases.

BCG Vaccine↗
PubMed2002

New vaccines for the prevention of tuberculosis.

Mycobacterium bovis, bacille Calmette-Guérin (BCG) is administered widely to newborns throughout the world and has been shown to be effective in preventing childhood tuberculosis but not reactivation pulmonary disease or human immunodeficiency virus-associated tuberculosis. Development of a more effective, better standardized, affordable vaccine with durable activity and fewer side effects is a major priority. Contemporary molecular techniques have identified promising immunodominant antigens and novel immunization strategies. Vaccine development has also been informed by an improved understanding of the role of nontuberculous mycobacteria in the efficacy of BCG and in the prevention of tuberculosis. Vaccines under investigation include attenuated or enhanced whole-cell live, whole-cell inactivated, subunit, DNA, and prime-boost vaccines. Several candidate vaccines have demonstrated activity in animal models that is equal to or superior to that of BCG, and human trials are under way. Because there is no identified surrogate marker for protection, identification of an improved vaccine will require long-term efficacy trials in humans.

BCG Vaccine↗
PubMed1997

Immunization of HIV-infected adults with a three-dose series of inactivated Mycobacterium vaccae.

Heat-killed Mycobacterium vaccae vaccine was administered in a 3-dose schedule to 12 HIV-infected adults with CD4 cell counts > or = 300/mm3. Local and systemic side effects were monitored. Delayed-type hypersensitivity to purified protein derivative and Mycobacterium avium sensitin was measured at baseline and after the final dose. Antibody to aralipoarabinomannin, man-lipoarabinomannin, and a short-term culture filtrate of Mycobacterium tuberculosis were also measured. Lymphocyte proliferation responses to M avium sensitin and M vaccae sonicate were determined. Vaccine site induration was maximal at 2 days (median, 6 mm) and no systemic side effects were noted. Purified protein derivative skin test conversions did not occur. Changes in CD4 counts and HIV viral load were not significant. Three (27%) of 11 subjects who completed the trial showed either M avium skin test (n = 1) or short-term culture filtrate antibody (n = 2) responses. A three-dose schedule of M vaccae vaccine is safe and well tolerated in adults with early HIV infection and produces detectable immunologic responses in a subset of these subjects.

AIDS-Related Opportunistic Infections↗
PubMed1996

The international epidemiology of disseminated Mycobacterium avium complex infection in AIDS. International MAC Study Group.

OBJECTIVE: To determine rates of disseminated Mycobacterium avium complex (MAC) infection among AIDS patients in developed and developing countries, and to determine whether different rates reflect differences in exposure or immunity, or both. DESIGN: Prospective cohort study. SETTING: University hospitals and outpatient AIDS programs. METHODS: HIV-infected subjects with CD4 counts < 200 x 10(6)/l were interviewed and had CD4 lymphocyte counts, blood cultures for mycobacteria (baseline and at 6 months), and skin tests with purified protein derivative (PPD) and M. avium sensitin. RESULTS: Among 566 study patients rates of disseminated MAC were 10.5-21.6% in New Hampshire, Boston and Finland compared to 2.4-2.6% in Trinidad and Kenya (P < 0.001). PPD skin test reactions > or = 5 mm were present in 20% of patients from Kenya compared to 1% at other sites (P < 0.001). Among patients from the United States and Finland, multiple logistic regression indicated that occupational exposure to soil and water was associated with a decreased risk of disseminated MAC, whereas the following were associated with an increased risk of disseminated MAC: low CD4 count, swimming in an indoor pool, history of bronchoscopy, regular consumption of raw or partially cooked fish/shellfish and treatment with granulocyte colony-stimulating factor. CONCLUSIONS: Rates of disseminated MAC in AIDS are higher in developed than developing countries and are due to both differences in exposure and differences in immunity. These data provide a rationale for prevention of MAC through both active immunization and reduction in exposure to the organism.

AIDS-Related Opportunistic Infections↗